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Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat

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Abstract

Rationale

Antipsychotic drugs, particularly the newer atypical compounds, have been associated with rapid weight gain in a clinical setting. However, there are few reported animal models producing reliable hyperphagia correlating with the human weight gain liability of these drugs.

Objective

To compare the effects of the classic neuroleptic haloperidol with the atypical antipsychotics clozapine and olanzapine on the microstructure of ingestive behaviour in rats.

Methods

Male hooded Lister rats drank a palatable high-calorie fat emulsion (10% Intralipid) during 30-min test sessions and microstructural analyses were made following administration of each drug over a range of doses.

Results

Clozapine (0.3 mg/kg) and olanzapine (0.1, 0.3, 1 mg/kg) significantly increased intake, whilst haloperidol (0.05, 0.1, 0.2 mg/kg) significantly decreased drinking. No significant changes in the latency to the first lick were observed following any of the drugs tested. Median interlick intervals showed small, dose-related increases after clozapine (3.0 mg/kg), olanzapine (0.3, 1.0 mg/kg) and haloperidol (0.1, 0.2 mg/kg). Olanzapine (1.0 mg/kg) significantly elevated the number of clusters of licking (bouts of licking separated by pauses greater than 500 ms), whilst clozapine and haloperidol did not. Mean cluster size (licks per cluster) was not affected by clozapine or olanzapine, but haloperidol (0.025, 0.05, 0.1, 0.2 mg/kg) produced marked, significant decreases in cluster size.

Conclusions

Clozapine and olanzapine increased fat intake whereas haloperidol did not, and this resembles the greater weight gain liability of atypical antipsychotics in humans. A delay or reduction of the post-ingestive satiety signal combined with preserved palatability appears to be the mechanism responsible for fat hyperphagia in rats treated with clozapine and olanzapine. Conversely, haloperidol leaves satiety unaffected but reduces the palatability of the fat emulsion resulting in reduced intake.

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References

  • Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ (1999) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156:1686–1696

    CAS  PubMed  Google Scholar 

  • Asin KE, Davis JD, Bednarz L (1992) Differential effects of the serotonergic and catecholaminergic drugs on ingestive behavior. Psychopharmacology 109:415–421

    CAS  PubMed  Google Scholar 

  • Baptista T (1999) Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand 100:3–16

    CAS  PubMed  Google Scholar 

  • Baptista T, Parada MA, Hernandez L (1987) Long-term administration of some antipsychotic drugs increases body weight and feeding in rats: are dopamine D2 receptors involved? Pharmacol Biochem Behav 27:399–405

    Google Scholar 

  • Baptista T, Mata A, Teneud L, De Quijada M, Han HW, Hernandez L (1993) Effects of long-term administration of clozapine on body weight and food intake in rats. Pharmacol Biochem Behav 45:51–54

    Article  PubMed  Google Scholar 

  • Basson BR, Kinon BJ, Taylor CC, Szymanski KA, Gilmore JA, Tollefson GD (2001) Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol or risperidone. J Clin Psychiatry 62:231–238

    PubMed  Google Scholar 

  • Beasley CM, Tollefson G, Tran P, Satterlee W, Sanger T, Hamilton S (1996) Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 14:111–123

    CAS  PubMed  Google Scholar 

  • Benvenga MJ, Leander JD (1997) Increased food consumption by clozapine, but not by olanzapine, in satiated rats. Drug Dev Res 41:48–50

    Article  Google Scholar 

  • Brown S, Birtwistle J, Roe L, Thompson C (1999) The unhealthy lifestyle of people with schizophrenia. Psychol Med 29:697–701

    Article  PubMed  Google Scholar 

  • Clifton PG, Lee MD, Dourish CT (2000) Similarities in the action of Ro 60-0175, a 5-HT2C receptor agonist, and d-fenfluramine on feeding patterns in the rat. Psychopharmacology 152:256–267

    CAS  PubMed  Google Scholar 

  • Davis JD (1973) The effectiveness of some sugars in stimulating licking behaviour in the rat. Physiol Behav 11:39–45

    CAS  PubMed  Google Scholar 

  • Davis JD, Perez MC (1993) Food deprivation-and palatability-induced microstructural changes in ingestive behavior. Am J Physiol 264 (Reg Int Comp Physiol 33):R97–R103

    PubMed  Google Scholar 

  • Davis JD, Smith GP (1992) Analysis of the microstructure of the rhythmic tongue movements of rats ingesting maltose and sucrose solutions. Behav Neurosci 106:217–228

    CAS  PubMed  Google Scholar 

  • Dourish CT (1995) Multiple serotonin receptors: opportunities for new treatments for obesity? Obesity Res 3:449S–462S

    CAS  Google Scholar 

  • Esel E, Basturk M, Saffet Gonul A, Kula M, Tayfun Turan M, Yabanoglu I, Sofuoglu S (2001) Effects of olanzapine and haloperidol on serum prolactin levels in male schizophrenic patients. Psychoneuroendocrinology 26:641–647

    Article  PubMed  Google Scholar 

  • Garattini S, Mennini T, Samanin R (1989) Reduction of food intake by manipulation of central serotonin: current experimental results. Br J Psychiatry 155:41–51

    Google Scholar 

  • Geary N, Smith GP (1985) Pimozide decreases the positive reinforcing effect of sham fed sucrose in the rat. Pharmacol Biochem Behav 22:787–790

    Article  PubMed  Google Scholar 

  • Goodall E, Oxtoby C, Richards R, Watkinson G, Silverstone T (1988) A clinical trial of the efficacy and acceptability of d-fenfluramine in the treatment of neuroleptic-induced obesity. Br J Psychiatry 153:208–213

    PubMed  Google Scholar 

  • Howell DC (1997) Statistical methods for psychology, 4th edn. Duxbury Press, London

  • Kapur S, Barsoum SC, Seeman MD (2000) Dopamine D2 receptor blockade by haloperidol: 3H-raclopride reveals much higher occupancy than EEDQ. Neuropsychopharmacology 23:595–598

    Article  PubMed  Google Scholar 

  • Kraus T, Haack M, Schuld A, Hinze-Selch D, Kuhn M, Uhr M, Pollmacher T (1999) Body weight regulation and leptin plasma levels during treatment with antipsychotic drugs. Am J Psychiatry 156:312–314

    CAS  PubMed  Google Scholar 

  • Lecklin A, Etu-Seppala P, Stark H, Tuomisto L (1998) Effects of intracerebroventricularly infused histamine and selective H1, H2 and H3 agonists on food and water intake and urine flow in Wistar rats. Brain Res 793:279–288

    Article  CAS  PubMed  Google Scholar 

  • Lee MD, Clifton PG (1992) Partial reversal of fluoxetine anorexia by the 5-HT antagonist metergoline. Psychopharmacology 107:359–364

    CAS  PubMed  Google Scholar 

  • Lee MD, Clifton PG (2002) Meal patterns of free feeding rats treated with clozapine, olanzapine or haloperidol. Pharmacol Biochem Behav 71:147–154

    Article  PubMed  Google Scholar 

  • Moore NA, Bymaster FP (1999) Neuropharmacological profiles of novel antipsychotic agents. In: Palomo T, Beninger RJ, Archer T (eds) Interactive monoaminergic disorders, strategies for studying brain disorders 4. Editorial Sintesis, Madrid

  • Remington G, Kapur S (2000) Atypical antipsychotics: are some more atypical than others? Psychopharmacology 148:3–15

    CAS  PubMed  Google Scholar 

  • Rossi R, Del Prete E, Scharrer E (1999) Effect of the H1-histamine receptor agonist betahistine on drinking and eating behaviour in pygmy goats. Physiol Behav 66:517–521

    Article  PubMed  Google Scholar 

  • Spector AC, Klumpp PA, Kaplan JM (1998) Analytical issues in the evaluation of food deprivation and sucrose concentration effects of the microstructure of licking behaviour in the rat. Behav Neurosci 112:678–694

    CAS  PubMed  Google Scholar 

  • Stanton JM (1995) Weight gain associated with neuroleptic medication: a review. Schizophr Bull 21:463–472

    CAS  PubMed  Google Scholar 

  • Vickers SP, Dourish, CT, Kennett GA (2001) Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 41:200–209

    CAS  PubMed  Google Scholar 

  • Ward BO, Somerville EM, Clifton PG (2000) Intraccumbens baclofen selectively enhances feeding behaviour in the rat. Physiol Behav 68:463–468

    Article  PubMed  Google Scholar 

  • Warwick ZS, Schiffman SS (1992) Role of dietary fat in calorie intake and weight gain. Neurosci Biobehav Rev 16:585–596

    Google Scholar 

  • Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J, Mintz J, Marder SR (1999) Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychol 60:358–363

    CAS  Google Scholar 

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Acknowledgements

A.W.H. is supported by an MRC Collaborative Studentship with Eli Lilly & Co.

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Authors and Affiliations

  1. Laboratory of Experimental Psychology, University of Sussex, Brighton, BN1 9QG, UK

    Abegale W. Hartfield & Peter G. Clifton

  2. Eli Lilly & Co, Erl Wood Manor, Windlesham, GU20 6PH, UK

    Nicholas A. Moore

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  1. Abegale W. Hartfield
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  2. Nicholas A. Moore
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  3. Peter G. Clifton
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Correspondence to Peter G. Clifton.

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Hartfield, A.W., Moore, N.A. & Clifton, P.G. Effects of clozapine, olanzapine and haloperidol on the microstructure of ingestive behaviour in the rat. Psychopharmacology 167, 115–122 (2003). https://doi.org/10.1007/s00213-002-1368-8

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  • DOI: https://doi.org/10.1007/s00213-002-1368-8

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